EP0393109A1 - Novel 2,3-thiomorpholinedione-2-oxime derivatives, pharmaceutical compositions containing them and process for preparing same. - Google Patents
Novel 2,3-thiomorpholinedione-2-oxime derivatives, pharmaceutical compositions containing them and process for preparing same.Info
- Publication number
- EP0393109A1 EP0393109A1 EP89900294A EP89900294A EP0393109A1 EP 0393109 A1 EP0393109 A1 EP 0393109A1 EP 89900294 A EP89900294 A EP 89900294A EP 89900294 A EP89900294 A EP 89900294A EP 0393109 A1 EP0393109 A1 EP 0393109A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- group
- alkyl
- alkoxy
- halogen
- substituted
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- ITYCYKLXTLAVTD-UHFFFAOYSA-N 2-hydroxyiminothiomorpholin-3-one Chemical class ON=C1SCCNC1=O ITYCYKLXTLAVTD-UHFFFAOYSA-N 0.000 title claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 6
- 238000004519 manufacturing process Methods 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 34
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 26
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 20
- 150000002367 halogens Chemical group 0.000 claims abstract description 19
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 13
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 12
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 12
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 8
- -1 cyano, amino Chemical group 0.000 claims abstract description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 7
- 125000001424 substituent group Chemical group 0.000 claims abstract description 7
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims abstract description 6
- 125000002252 acyl group Chemical group 0.000 claims abstract description 6
- 125000003282 alkyl amino group Chemical group 0.000 claims abstract description 6
- 125000004663 dialkyl amino group Chemical group 0.000 claims abstract description 6
- 125000004185 ester group Chemical group 0.000 claims abstract description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 6
- 239000001257 hydrogen Substances 0.000 claims abstract description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 6
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 6
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims abstract description 6
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 8
- 239000003960 organic solvent Substances 0.000 claims description 7
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- 150000007530 organic bases Chemical class 0.000 claims description 4
- 150000003512 tertiary amines Chemical class 0.000 claims description 4
- 150000007529 inorganic bases Chemical class 0.000 claims description 3
- 229910000000 metal hydroxide Inorganic materials 0.000 claims description 3
- 150000004692 metal hydroxides Chemical class 0.000 claims description 3
- 150000004703 alkoxides Chemical class 0.000 claims description 2
- 238000009835 boiling Methods 0.000 claims description 2
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 claims description 2
- 125000005905 mesyloxy group Chemical group 0.000 claims description 2
- 125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims 2
- 239000000654 additive Substances 0.000 claims 2
- 239000000969 carrier Substances 0.000 claims 2
- 150000002576 ketones Chemical class 0.000 claims 2
- 239000004215 Carbon black (E152) Substances 0.000 claims 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims 1
- 150000001412 amines Chemical class 0.000 claims 1
- 229930195733 hydrocarbon Natural products 0.000 claims 1
- 150000002430 hydrocarbons Chemical class 0.000 claims 1
- 230000001131 transforming effect Effects 0.000 claims 1
- 208000007107 Stomach Ulcer Diseases 0.000 abstract description 4
- 208000000718 duodenal ulcer Diseases 0.000 abstract description 3
- 230000002496 gastric effect Effects 0.000 abstract description 3
- 230000002401 inhibitory effect Effects 0.000 abstract description 3
- 230000001120 cytoprotective effect Effects 0.000 abstract description 2
- 230000009858 acid secretion Effects 0.000 abstract 1
- 239000000126 substance Substances 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 230000010933 acylation Effects 0.000 description 4
- 238000005917 acylation reaction Methods 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- TULKOBWQIRTXSH-UHFFFAOYSA-N 3-benzyl-2-(nitromethylidene)-1,3-thiazolidine Chemical class [O-][N+](=O)C=C1SCCN1CC1=CC=CC=C1 TULKOBWQIRTXSH-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 208000025865 Ulcer Diseases 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 230000027119 gastric acid secretion Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 231100000397 ulcer Toxicity 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- FMPVUIWQJVRMBM-UHFFFAOYSA-N 4-benzyl-2-hydroxyiminothiomorpholin-3-one Chemical compound O=C1C(=NO)SCCN1CC1=CC=CC=C1 FMPVUIWQJVRMBM-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D279/10—1,4-Thiazines; Hydrogenated 1,4-thiazines
- C07D279/12—1,4-Thiazines; Hydrogenated 1,4-thiazines not condensed with other rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
Definitions
- This invention relates to novel 2 ,3-thiomorpolinedione-2-oxime-derivatives of the general formula (I),
- R 1 stands for hydrogen, halogen, C 1-4 alkyl, C 1-4 alkoxy or nitro group
- R 2 e ans a C 1-7 alkyl group optionally substituted by: hydroxyl or oxo group; or an ester group containing 1 to 4 carbon atoms in the alkoxy moiety; or a C 1-4 alkoxy. cyano, amino, C 1-4 alkylamino, or dialkylamino group; or an acyl group containing 1 to 7 carbon atoms in the alkyl moiety; or R 2 means an aryl-C 1-7 alkyl group optionally bearing the substituents defined above for R 2 in the alkyl chain and optionally substituted by halogen, nitro, C 1-4 alkyl or alkoxy group in the benzene ring; or R 2 represents an allyl, phenylallyl or phenylsulfonyl group, both latter groups optionally being substituted by halogen or a C 1-4 alkyl group in the benzene ring; or R 2 stands for a carbamoyl group substituted by one or two C
- the compounds of the general formula (I) have interesting cytoprotective and gastric acid secretion-inhibiting properties and are effective against gastric and duodenal ulcers.
- the aim of the present invention was to find novel, therapeutically useful compounds which can be prepared economically on an industrial scale, too. Accordingly the invention relates also to a process for the preparation of the new compounds of general formula (I),
- R 1 stands for hydrogen, halogen, C 1-4 alkyl, C 1-4 alkoxy or nitro group
- R 2 means a C 1 _ 7 alkyl group optionally substituted by: a hydroxyl or oxo group; or an ester group containing 1 to 4 carbon atoms in the alkoxy moiety; or a C 1-4 alkoxy, cyano, amino, C 1-4 alkylamino, or dialkylamino group; or an acyl group containing 1 to 7 carbon atoms in the alkyl moiety; or
- R 2 means an aryl-C 1-7 alkyl group optionally bearing the substituents defined above for R 2 in the alkyl chain and optionally substituted by halogen, nitro, C 1-4 alkyl or alkoxy group in the benzene ring; or
- R 2 represents an allyl, phenylallyl or phenylsulfonyl group, both latter groups optionally being substituted by halogen or a C 1-4 alkyl group in the benzene ring; or
- R 2 stands for a carbamoyl group substituted by one or two C 1-4 alkyl group(s) or phenyl group on the nitrogen atom which comprises a ) to obtain compoun ds of the gener a l f ormu l a (I) containing as R 2 a substituent different from an N ⁇
- R 3 has the same meaning as R 2 , except the N-substituted carbamoyl group and X is halogen or, when the meaning of R 3 is different from an acylatable group, X may be also a mesyloxy or tosyloxy group; or b) to obtain compounds of the general formula (I) containing an N-substituted cabamoyl group as R 2 , reacting a compound of the general formula (II), wherein R 1 is as defined above, in an inert organic solvent in the presence of an organic tertiary amine, preferably triethylamine with a compound of the general formula (IV), R 4 - NCO
- R 4 stands for a phenyl or C 1-4 alkyl group.
- the compounds according to the present invention can be prepared by the methods discussed hereinafter: a) a substitution alkylation or acylation is carried out the using a compound of the general formula (III), wherein R 3 is the same as R 2 , except any N-substituted cabamoyl group; and b) an addition acylation is performed by using a compound of the general formula (IV); in this case R 2 stands for an N-substituted cabamoyl group.
- the reaction is usually carried out in an organic solvent, preferably in methanol, ethanol, acetone or in an ether-type solvent, such as dioxane; or in acetonitrile, dimethylformamide or dimethylsulfoxide.
- organic solvent preferably in methanol, ethanol, acetone or in an ether-type solvent, such as dioxane; or in acetonitrile, dimethylformamide or dimethylsulfoxide.
- Alkaline metal hydroxides, carbonates, alkoxides or organic bases such as tertiary amines may be used as acid binding agents.
- the reaction is usually carried out at a temperature corresponding to the boiling point of the solvent used. After filtering off the precipitated salt, the product is isolated by evaporating the reaction mixture and then purified by a method known per se.
- Suitable catalysts are organic tertiary amine bases, preferably triethylamine.
- the reaction temperature may be varied between 0 °C and 100 °C.
- 4-phenylmethyl-0-methyl-2,3-thiomorpholinedione-2-oxime exerts a particularly advantageous effect based on the pharmacological inventigations.
- This compound shows a gastric acid secretion-inhibiting action with an oral ED 50 value of 20 mg/kg in the so-called Shay's rats, is effective also against stress-induced ulcers with an oral ED 50 value of 71 mg/kg and against acidic ethanol-induced gastric ulcers with an oral ED 50 value of 7 mg/kg.
- Example 1 General Example for the substitution alkylation or acylation, respectively
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
La présente invention se rapporte à de nouveaux composés représentés par la formule générale (I), où R1 représente un groupe hydrogène, halogène, C1-4 alkyle, C1-4 alkoxy ou nitro; R2 représente un groupe C1-7 alkyle éventuellement substitué par: un groupe hydroxyle ou oxo; ou un groupe ester contenant 1 à 4 atomes de carbone dans la fraction alkoxy; ou un groupe C1-4 alkoxy, cyano, amino, C1-4 alkylamino ou dialkylamino; ou un groupe acyle contenant 1 à 7 atomes de carbone dans la fraction alkyle; ou R2 représente un groupe aryl-C1-7 alkyle portant éventuellement les substituants définis ci-dessus pour R2 dans la chaîne alkyle et éventuellement substitué par un groupe halogène, nitro, C1-4 alkyle ou alkoxy dans l'anneau de benzène; ou R2 représente un groupe allyle, phénylallyle ou phénylsulfonyle, ces deux derniers groupes étant éventuellememt substitués par un halogène ou par un groupe C1-4 alkyle dans l'anneau de benzène; ou R2 représente un groupe carbamoyle substitué par un ou deux groupe(s) C1-4 alkyle ou par un groupe phényle sur l'atome d'azote. Les composés de la présente invention exercent une action cytoprotectrice et d'inhibition de la sécrétion d'acide et sont par conséquent efficaces contre les ulcères gastriques et duodénaux.The present invention relates to new compounds represented by the general formula (I), where R1 represents a hydrogen, halogen, C1-4 alkyl, C1-4 alkoxy or nitro group; R2 represents a C1-7 alkyl group optionally substituted by: a hydroxyl or oxo group; or an ester group containing 1 to 4 carbon atoms in the alkoxy moiety; or a C1-4 alkoxy, cyano, amino, C1-4 alkylamino or dialkylamino group; or an acyl group containing 1 to 7 carbon atoms in the alkyl moiety; or R2 represents an aryl-C1-7 alkyl group optionally carrying the substituents defined above for R2 in the alkyl chain and optionally substituted by a halogen, nitro, C1-4 alkyl or alkoxy group in the benzene ring; or R2 represents an allyl, phenylallyl or phenylsulfonyl group, the latter two groups being optionally substituted by a halogen or by a C1-4 alkyl group in the benzene ring; or R2 represents a carbamoyl group substituted by one or two C1-4 alkyl group (s) or by a phenyl group on the nitrogen atom. The compounds of the present invention exert a cytoprotective and inhibitory action on acid secretion and are therefore effective against gastric and duodenal ulcers.
Description
Claims
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AT89900294T ATE103279T1 (en) | 1987-12-14 | 1989-07-05 | 2,3-THIOMORPHOLINEDIONE-2-OXIME DERIVATIVES, MEDICINAL COMPOSITIONS AND METHOD OF MANUFACTURE. |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
HU875630A HU199134B (en) | 1987-12-14 | 1987-12-14 | Process for producing new 2,3-thiomorpholinedine-2-oxime derivatives and pharmaceutical compositions comprising same |
HU563087 | 1987-12-14 |
Publications (2)
Publication Number | Publication Date |
---|---|
EP0393109A1 true EP0393109A1 (en) | 1990-10-24 |
EP0393109B1 EP0393109B1 (en) | 1994-03-23 |
Family
ID=10970505
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP89900294A Expired - Lifetime EP0393109B1 (en) | 1987-12-14 | 1989-07-05 | Novel 2,3-thiomorpholinedione-2-oxime derivatives, pharmaceutical compositions containing them and process for preparing same |
Country Status (8)
Country | Link |
---|---|
US (1) | US5106846A (en) |
EP (1) | EP0393109B1 (en) |
JP (1) | JPH03502688A (en) |
KR (1) | KR920009884B1 (en) |
CN (1) | CN1016689B (en) |
DE (1) | DE3888697T2 (en) |
HU (1) | HU199134B (en) |
WO (1) | WO1989005805A1 (en) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6423708B1 (en) | 1996-09-30 | 2002-07-23 | Pfizer Inc | Aralkyl and aralkylidene heterocyclic lactams and imides |
UA56185C2 (en) | 1996-09-30 | 2003-05-15 | Пфайзер Інк. | Aralkyl- and aralkylidene heterocyclic lactams and imids, a pharmaceutical composition and a treatment method |
JP5955339B2 (en) | 2011-01-28 | 2016-07-20 | ビーエーエスエフ ソシエタス・ヨーロピアBasf Se | Polymerizable composition containing oxime sulfonate as thermosetting agent |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3883510A (en) * | 1971-08-12 | 1975-05-13 | Du Pont | Carbamate esters of 2-oxyimino-3-keto-1,4-diheterocyclics |
US3790566A (en) * | 1971-08-12 | 1974-02-05 | Du Pont | Carbamate esters of 2-oxyimino-3-keto-1,4-diheterocyclics |
US4003895A (en) * | 1972-12-29 | 1977-01-18 | Union Carbide Corporation | 1,4-Thiazines |
US3894150A (en) * | 1972-12-29 | 1975-07-08 | Union Carbide Corp | Carbamate pesticidal compositions |
US3930002A (en) * | 1972-12-29 | 1975-12-30 | Jr John Apling Durden | Carbamate pesticidal compositions |
US4003897A (en) * | 1974-06-07 | 1977-01-18 | Union Carbide Corporation | Carbamate pesticidal compounds |
US4327110A (en) * | 1977-03-28 | 1982-04-27 | Union Carbide Corporation | Pesticidal symmetrical N-substituted bis-carbamoyloximino disulfide compounds |
JPS61113437A (en) * | 1984-09-11 | 1986-05-31 | ゼテク・インコ−ポレ−テツド | Method and apparatus for foreknowing ovulation of woman |
-
1987
- 1987-12-14 HU HU875630A patent/HU199134B/en not_active IP Right Cessation
-
1988
- 1988-12-13 WO PCT/HU1988/000080 patent/WO1989005805A1/en active IP Right Grant
- 1988-12-13 US US07/477,999 patent/US5106846A/en not_active Expired - Fee Related
- 1988-12-13 JP JP1500414A patent/JPH03502688A/en active Pending
- 1988-12-13 DE DE3888697T patent/DE3888697T2/en not_active Expired - Fee Related
- 1988-12-13 KR KR1019890701523A patent/KR920009884B1/en not_active IP Right Cessation
- 1988-12-13 CN CN88108569A patent/CN1016689B/en not_active Expired
-
1989
- 1989-07-05 EP EP89900294A patent/EP0393109B1/en not_active Expired - Lifetime
Non-Patent Citations (1)
Title |
---|
See references of WO8905805A1 * |
Also Published As
Publication number | Publication date |
---|---|
WO1989005805A1 (en) | 1989-06-29 |
KR900700471A (en) | 1990-08-13 |
HU199134B (en) | 1990-01-29 |
DE3888697T2 (en) | 1994-07-07 |
DE3888697D1 (en) | 1994-04-28 |
HUT49127A (en) | 1989-08-28 |
KR920009884B1 (en) | 1992-11-05 |
EP0393109B1 (en) | 1994-03-23 |
CN1016689B (en) | 1992-05-20 |
CN1034927A (en) | 1989-08-23 |
US5106846A (en) | 1992-04-21 |
JPH03502688A (en) | 1991-06-20 |
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